Proton pump inhibitors for upper gastrointestinal bleeding
Introduction
Acute upper gastrointestinal bleeding (UGIB) remains a common cause of hospitalization with an annual incidence of 78/100′000 population and a reported mortality that decreased in the United States over the last 2 decades from 4.7% to 2.1% [1,2]. UGIB can be categorized into variceal and non-variceal UGIB (NVUGIB) causes, as there are important differences in management strategies. Peptic ulcer (PU) disease remains the most common cause of NVUGIB and hospital admission diagnosis in 2012 among all gastro-intestinal related disorders in the United States [3]. Despite advances in modern day management of UGIB, including optimized use of endoscopic therapy, the morbidity and mortality associated with UGIB remains significant, as does its health economic burden [1,2,4,5]. Medical therapy is an attractive adjuvant to endoscopic treatment in UGIB and acid suppression with the use of high-dose proton pump inhibitors (PPI) remains a cornerstone in the medical management of acute UGIB; the optimal route of administration and dosing however remain controversial [6].
This review summarizes the protective pathophysiological mechanisms and the current evidence pertaining to the efficacy and cost-effectiveness of PPI therapy in the management of UGIB. It will discuss the timing, dosage and the route of administration of PPI during the initial management of UGIB prior and immediately following, as well as in the short-term following discharge.
Section snippets
Proton pump inhibitor and the role of acid suppression
In vitro data have explored the important role of acid in impairing hemostasis and causing clot digestion [7], highlighting the important therapeutic role of acid suppressive drugs in the acute setting of UGIB. Maintenance of a high intragastric pH (above 6.0) during the management of UGIB is indeed warranted, as the ability for platelets to form the primary hemostatic platelet plug is deeply impaired by an acid environment, being reduced by 75% at a pH of 6.8 relative to a pH of 7.4. When the
PPI prior endoscopy
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PPI started prior to endoscopy only decrease the proportion of patients with high-risk stigmata ulcers and the requirement for endoscopic treatment but do not affect rebleeding or mortality
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If endoscopic evaluation has to be delayed or cannot be performed, PPI therapy should be started and continued to reduce the risk of further bleeding.
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When PPI are considered, the high dose iv (80 mg) followed by 8 mg/h should be the preferred regimen
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Additional data are required to better determine the
Practice points
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Authoritative guidelines support use of high dose PPI for 3 days after successful endoscopic hemostasis for NVUGIB, in particular high risk peptic ulcer bleeding
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Additional data are required to prove non-inferiority, let alone equivalence of intermittent (oral/iv) dosing in comparison to continuous infusion of PPI
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PPI after endoscopy in NVUGIB is a dominant strategy in economic terms, i.e.: more efficacious and less costly
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In variceal UGIB, only a short 10-day course of a once-daily oral PPI
Conclusion
Adherence to evidence-based practice and ensuring robust quality assurance of UGIB management are crucial for optimizing patient outcomes (Fig. 2). Clear guidelines for adequate PPI use in order to standardize best practices are urgenty required. Although high-dose PPI after endoscopy is unanimously incorporated into guidelines for management of NVUGIB, many gaps persist in our knowledge of best practice for PPI use prior endoscopy and to determine the optimal dosing regimen once the iv regimen
Research agenda
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Cost effectiveness analysis for PPI use prior endoscopy and better identify who can benefit
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Additional trials to assess whether intermittent regimens are equivalent to continuous iv PPI use
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To determine the optimal dosing regimen once the iv PPI regimen is completed in patients with acute NVUGIB undergoing successful hemostasis
Conflicts of interest
None.
References (50)
- et al.
Hospitalization and mortality rates from peptic ulcer disease and GI bleeding in the 1990s: relationship to sales of nonsteroidal anti-inflammatory drugs and acid suppression medications
Am J Gastroenterol
(2002) - et al.
The in-hospital mortality rate for upper GI hemorrhage has decreased over 2 decades in the United States: a nationwide analysis
Gastrointest Endosc
(2015) - et al.
Effect of acid and pepsin on blood coagulation and platelet aggregation. A possible contributor prolonged gastroduodenal mucosal hemorrhage
Gastroenterology
(1978) - et al.
Cost-effectiveness analysis of high-dose omeprazole infusion before endoscopy for patients with upper-GI bleeding
Gastrointest Endosc
(2008) - et al.
Cost-effectiveness of proton-pump inhibition before endoscopy in upper gastrointestinal bleeding
Clin Gastroenterol Hepatol
(2008) - et al.
Proton pump inhibitor therapy for peptic ulcer bleeding: Cochrane collaboration meta-analysis of randomized controlled trials
Mayo Clin Proc
(2007) Should every patient with suspected upper GI bleeding receive a proton pump inhibitor while awaiting endoscopy?
Gastrointest Endosc
(2008)- et al.
Endoscopic therapy for bleeding ulcers: an evidence-based approach based on meta-analyses of randomized controlled trials
Clin Gastroenterol Hepatol
(2009) - et al.
Cost-effectiveness analysis of high-dose omeprazole infusion as adjuvant therapy to endoscopic treatment of bleeding peptic ulcer
Gastrointest Endosc
(2003) - et al.
Complications of proton pump inhibitor therapy
Gastroenterology
(2017)
Potential costs of inappropriate use of proton pump inhibitors
Am J Med Sci
The appropriate use of proton pump inhibitors (PPIs): need for a reappraisal
Eur J Intern Med
Burden of gastrointestinal, liver, and pancreatic diseases in the United States
Gastroenterology
Epidemiology and outcome of patients hospitalized with acute lower gastrointestinal hemorrhage: a population-based study
Am J Gastroenterol
Rolling review: upper gastrointestinal bleeding
Aliment Pharmacol Ther
Comparison of different regimens of proton pump inhibitors for acute peptic ulcer bleeding
Cochrane Database Syst Rev
Clot lysis by gastric juice: an in vitro study
Gut
Review article: acid suppression in non-variceal acute upper gastrointestinal bleeding
Aliment Pharmacol Ther
International consensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding
Ann Intern Med
CLINICAL PRACTICE. Upper gastrointestinal bleeding due to a peptic ulcer
N Engl J Med
25 Years of proton pump inhibitors: a comprehensive review
Gut Liver
Intermittent vs continuous proton pump inhibitor therapy for high-risk bleeding ulcers: a systematic review and meta-analysis
JAMA Intern Med
Omeprazole before endoscopy in patients with gastrointestinal bleeding
N Engl J Med
Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding
Cochrane Database Syst Rev
Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: european society of gastrointestinal endoscopy (ESGE) guideline
Endoscopy
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